Neural multimodal integration underlying synchronization with a co-performer in music: influences of motor expertise and visual information

Sensorimotor synchronization is a general skill that musicians have developed to the highest levels of performance, including synchronization in timing and articulation. This study investigated neurocognitive processes that enable such high levels of performance, specifically testing the relevance of 1) motor resonance and sharing high levels of motor expertise with the co-performer, and 2) the role of visual information in addition to auditory information. Musicians with varying levels of piano expertise (including non-pianists) performed on a single piano key with their right hand along with recordings of a pianist who performed simple melodies with the left hand, synchronizing timing and articulation. The prerecorded performances were presented as audio-only, audio-video, or audio-animation stimuli. Double pulse Transcranial Magnetic Stimulation (dTMS) was applied to test the contribution of the right dorsal premotor cortex (dPMC), an area implicated in motor resonance with observed (left-hand) actions, and the contribution of the right intraparietal sulcus (IPS), an area known for multisensory binding. Results showed effects of dTMS in the conditions that included visual information. IPS stimulation improved synchronization ability, although this effect was found to reverse for the video condition with higher levels of relevant motor expertise. dPMC stimulation improved or worsened synchronization ability. Level of relevant motor expertise was found to influence this direction in the video condition. These results indicate that high levels of relevant motor expertise are required to beneficially employ visual and motor information of a co-performer for sensorimotor synchronization, which may qualify the effects of dPMC and IPS involvement

Artery tertiary lymphoid organs control aorta immunity and protect against atherosclerosis via vascular smooth muscle cell lymphotoxin β receptors

Tertiary lymphoid organs (TLOs) emerge during nonresolving peripheral inflammation, but their impact on disease progression remains unknown. We have found in aged Apoe−/− mice that artery TLOs (ATLOs) controlled highly territorialized aorta T cell responses. ATLOs promoted T cell recruitment, primed CD4+ T cells, generated CD4+, CD8+, T regulatory (Treg) effector and central memory cells, converted naive CD4+ T cells into induced Treg cells, and presented antigen by an unusual set of dendritic cells and B cells. Meanwhile, vascular smooth muscle cell lymphotoxin β receptors (VSMC-LTβRs) protected against atherosclerosis by maintaining structure, cellularity, and size of ATLOs though VSMC-LTβRs did not affect secondary lymphoid organs: Atherosclerosis was markedly exacerbated in Apoe−/−Ltbr−/− and to a similar extent in aged Apoe−/−Ltbrfl/flTagln-cre mice. These data support the conclusion that the immune system employs ATLOs to organize aorta T cell homeostasis during aging and that VSMC-LTβRs participate in atherosclerosis protection via ATLOs

Designing new musical technologies for wellbeing – exploring the needs and preferences of those living with dementia

Background Music has been found to provide numerous health and wellbeing benefits for people living with dementia. It is also quite open in terms of the forms of engagement it affords, offering numerous different ways to listen, play and create. Although technology has the potential to reduce barriers that people with dementia face when attempting to engage with music, little has been designed with them in mind. This study seeks to understand: i) the needs, rewards, and barriers that people with dementia and their carers face when engaging with music in their daily lives, and ii) how any specifically designed future musical interfaces will look and react. Method A survey using a mixture of qualitative and quantitative questions was distributed online to people living with mild cognitive impairment or dementia and to those that provide care for them. Questions asked about motivations and contexts for engagement, barriers and enabling factors, the comparative importance of various musical activities, and the technologies people living with dementia currently use and why. Result The main tools for listening include smartphone apps, radio, virtual assistants, and YouTube. Most participants listen to music on multiple devices, with its ease of use, accessibility, and convenience for their current listening environment frequently influencing their choice. They also presented a wide range of motivations for engaging with music, but a majority of participants agreed that “feeling like myself” is their most important motivator. Most participants thought it was very important for devices to offer choice. It should also have a simple way for them to turn it off or switch to a safe song if they hear a distressing song or it experiences signal loss. Conclusion The findings highlight that people living with dementia have diverse individual motivations for music, and they want it to perform different functions at different times (e.g. sometimes aiding in their relaxation and sometimes connecting them with others). The findings point to fruitful future directions for technology development: i) ready-to-use tools that can adapt to changing interests, and ii) tools that make it easy to access choice and variety while safeguarding against distress from unwanted or unexpected events

Designing new musical technologies for wellbeing – exploring the needs and preferences of those living with dementia

Background Music has been found to provide numerous health and wellbeing benefits for people living with dementia. It is also quite open in terms of the forms of engagement it affords, offering numerous different ways to listen, play and create. Although technology has the potential to reduce barriers that people with dementia face when attempting to engage with music, little has been designed with them in mind. This study seeks to understand: i) the needs, rewards, and barriers that people with dementia and their carers face when engaging with music in their daily lives, and ii) how any specifically designed future musical interfaces will look and react. Method A survey using a mixture of qualitative and quantitative questions was distributed online to people living with mild cognitive impairment or dementia and to those that provide care for them. Questions asked about motivations and contexts for engagement, barriers and enabling factors, the comparative importance of various musical activities, and the technologies people living with dementia currently use and why. Result The main tools for listening include smartphone apps, radio, virtual assistants, and YouTube. Most participants listen to music on multiple devices, with its ease of use, accessibility, and convenience for their current listening environment frequently influencing their choice. They also presented a wide range of motivations for engaging with music, but a majority of participants agreed that “feeling like myself” is their most important motivator. Most participants thought it was very important for devices to offer choice. It should also have a simple way for them to turn it off or switch to a safe song if they hear a distressing song or it experiences signal loss. Conclusion The findings highlight that people living with dementia have diverse individual motivations for music, and they want it to perform different functions at different times (e.g. sometimes aiding in their relaxation and sometimes connecting them with others). The findings point to fruitful future directions for technology development: i) ready-to-use tools that can adapt to changing interests, and ii) tools that make it easy to access choice and variety while safeguarding against distress from unwanted or unexpected events

Dexfenfluramine and the oestrogen-metabolizing enzyme CYP1B1 in the development of pulmonary arterial hypertension

<p>Aims: Pulmonary arterial hypertension (PAH) occurs more frequently in women than men. Oestrogen and the oestrogen-metabolising enzyme cytochrome P450 1B1 (CYP1B1) play a role in the development of PAH. Anorectic drugs such as dexfenfluramine (Dfen) have been associated with the development of PAH. Dfen mediates PAH via a serotonergic mechanism and we have shown serotonin to up-regulate expression of CYP1B1 in human pulmonary artery smooth muscle cells (PASMCs). Thus here we assess the role of CYP1B1 in the development of Dfen-induced PAH.</p> <p>Methods and results: Dfen (5 mg kg−1 day−1 PO for 28 days) increased right ventricular pressure and pulmonary vascular remodelling in female mice only. Mice dosed with Dfen showed increased whole lung expression of CYP1B1 and Dfen-induced PAH was ablated in CYP1B1−/− mice. In line with this, Dfen up-regulated expression of CYP1B1 in PASMCs from PAH patients (PAH-PASMCs) and Dfen-mediated proliferation of PAH-PASMCs was ablated by pharmacological inhibition of CYP1B1. Dfen increased expression of tryptophan hydroxylase 1 (Tph1; the rate-limiting enzyme in the synthesis of serotonin) in PAH-PASMCs and both Dfen-induced proliferation and Dfen-induced up-regulation of CYP1B1 were ablated by inhibition of Tph1. 17β-Oestradiol increased expression of both Tph1 and CYP1B1 in PAH-PASMCs, and Dfen and 17β-oestradiol had synergistic effects on proliferation of PAH-PASMCs. Finally, ovariectomy protected against Dfen-induced PAH in female mice.</p> <p>Conclusion: CYP1B1 is critical in the development of Dfen-induced PAH in mice in vivo and proliferation of PAH-PASMCs in vitro. CYP1B1 may provide a novel therapeutic target for PAH.</p&gt

The aorta can act as a site of naïve CD4+ T-cell priming

Aims: Aortic adaptive immunity plays a role in atherosclerosis; however, the precise mechanisms leading to T-cell activation in the arterial wall remain poorly understood. Methods and results: Here, we have identified naïve T cells in the aorta of wild-Type and T-cell receptor transgenic mice and we demonstrate that naïve T cells can be primed directly in the vessel wall with both kinetics and frequency of T-cell activation found to be similar to splenic and lymphoid T cells. Aortic homing of naïve T cells is regulated at least in part by the P-selectin glycosylated ligand-1 receptor. In experimental atherosclerosis the aorta supports CD4+ T-cell activation selectively driving Th1 polarization. By contrast, secondary lymphoid organs display Treg expansion. Conclusion: Our results demonstrate that the aorta can support T-cell priming and that naïve T cells traffic between the circulation and vessel wall. These data underpin the paradigm that local priming of T cells specific for plaque antigens contributes to atherosclerosis progression

T cells are dominant population in human abdominal aortic aneurysms and their infiltration in the perivascular tissue correlates with disease severity

Abdominal Aortic Aneurysm (AAA) is a major cause of cardiovascular mortality. Adverse changes in vascular phenotype act in concert with chronic inflammation to promote AAA progression. Perivascular adipose tissue (PVAT) helps maintain vascular homeostasis but when inflamed and dysfunctional, can also promote vascular pathology. Previous studies suggested that PVAT may be an important site of vascular inflammation in AAA; however, a detailed assessment of leukocyte populations in human AAA, their anatomic location in the vessel wall and correlation to AAA size remain undefined. Accordingly, we performed in depth immunophenotyping of cells infiltrating the pathologically altered perivascular tissue (PVT) and vessel wall in AAA samples at the site of maximal dilatation (n=51 patients). Flow cytometry revealed that T cells, rather than macrophages, are the major leukocyte subset in AAA and that their greatest accumulations occur in PVT. Both CD4+ and CD8+ T cell populations are highly activated in both compartments, with CD4+ T cells displaying the highest activation status within the AAA wall. Finally, we observed a positive relationship between T cell infiltration in PVT and AAA wall. Interestingly, only PVT T cell infiltration was strongly related to tertiles of AAA size. In summary, this study highlights an important role for PVT as a reservoir of T lymphocytes and potentially as a key site in modulating the underlying inflammation in AAA

Influence of supramolecular forces on the linear viscoelasticity of gluten

Stress relaxation behavior of hydrated gluten networks was investigated by means of rheometry combined with μ-computed tomography (μ-CT) imaging. Stress relaxation behavior was followed over a wide temperature range (0–70 °C). Modulation of intermolecular bonds was achieved with urea or ascorbic acid in an effort to elucidate the presiding intermolecular interactions over gluten network relaxation. Master curves of viscoelasticity were constructed, and relaxation spectra were computed revealing three relaxation regimes for all samples. Relaxation commences with a well-defined short-time regime where Rouse-like modes dominate, followed by a power law region displaying continuous relaxation concluding in a terminal zone. In the latter zone, poroelastic relaxation due to water migration in the nanoporous structure of the network also contributes to the stress relief in the material. Hydrogen bonding between adjacent protein chains was identified as the determinant force that influences the relaxation of the networks. Changes in intermolecular interactions also resulted in changes in microstructure of the material that was also linked to the relaxation behavior of the networks

Distribution of lipids in the grain of wheat (cv Hereward) determined by lipidomic analysis of milling and pearling fractions

Lipidomic analyses of milling and pearling fractions from wheat grain were carried out to determine differences in composition which could relate to the spatial distribution of lipids in the grain. Free fatty acids and triacylglycerols were major components in all fractions, but the relative contents of polar lipids varied, particularly lysophosphatidyl choline and digalactosyldiglyceride, which were enriched in flour fractions. By contrast, minor phospholipids were enriched in bran and offal fractions. The most abundant fatty acids in the analysed acyl lipids were C16:0 and C18:2 and their combinations, including C36:4 and C34:2. Phospholipids and galactolipids have been reported to have beneficial properties for bread making, while free fatty acids and triacylglycerols are considered detrimental. The subtle differences in the compositions of fractions determined in the present study could therefore underpin the production of flour fractions with optimised compositions for different end uses